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Temporal Processing by Growth Factors in Memory Formation

Award Number: R01MH120300
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Temporal Processing by Growth Factors in Memory Formation - PROJECT SUMMARY/ABSTRACT A growing body of evidence suggests that growth factors (GFs), once considered to function mainly in development, also regulate synaptic plasticity and memory in the adult. This proposal reflects on an ongoing research program in our laboratory that has focused on the role of GFs in memory formation. The primary focus of this current project is to examine GF-mediated memory formation from a novel perspective, which takes into account the temporal aspect of their activity as part of the cellular computation involved in forming memories. Repeated-trial learning, a fundamental form of memory acquisition exhibited by virtually all animals, including man, requires a temporal interaction between an ongoing stimulus and the delayed effects of a previous stimulus. We will use a powerful paradigm to study repeated-trial training in the marine mollusk Aplysia, which develops long-term memory (LTM) for sensitization after only two training trials, but only if they are separated by a permissive and surprisingly specific time interval of ~45 min. This minimal system clearly separates the initiating stimulus (Trial 1) from the repeated stimulus (Trial 2), providing unparalleled access to the temporal interactions underlying repeated-trial LTM. We will investigate two GF-dependent mechanisms that our preliminary evidence suggests contribute significantly to temporal processing at the heart of repeated-trial learning. The first (explored in AIM 1) is a distributed mechanism for GF-dependent phosphorylation of extracellularly regulated kinase (ERK). The second mechanism (explored in AIM 2) is the multi-step signaling of a specific GF, TGFβ, which we propose similarly integrates the timing of training trials. Finally, in AIM 3 we will try to establish causal connections between the timing of single ERK phosphorylation, TGFβ availability, and the persistent effects of two-trial training The project holds promise for significant impact from both a basic scientific perspective and a clinical perspective. From a basic scientific perspective, Aplysia provides an exceptional experimental system that has the potential to demonstrate causal linkages between GF-mediated memory formation and its underlying synaptic and molecular mechanisms, while simultaneously exploring the temporal features of those mechanisms. And from a clinical perspective, the impact of this project addresses a major challenge in mental health: to understand and treat the devastating cognitive disorders that accompany neurodegenerative diseases. GF signaling has been directly implicated in many of these diseases and, since GFs are extracellular proteins, understanding when and where they act in the brain during memory formation could provide novel strategies for developing more specific and more effective therapeutic agents.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $476,413 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	5	8/15/2024	NON-COMPETING CONTINUATION	$47,641
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	5	11/16/2023	NON-COMPETING CONTINUATION	$428,772
														Subtotal = $476,413

Issue Date FY: 2023 ( Subtotal = $476,413 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	4	2/7/2023	NON-COMPETING CONTINUATION	$47,641
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	4	12/1/2022	NON-COMPETING CONTINUATION	$428,772
														Subtotal = $476,413

Issue Date FY: 2022 ( Subtotal = $476,413 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	3	11/5/2021	NON-COMPETING CONTINUATION	$428,772
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	3	5/23/2022	NON-COMPETING CONTINUATION	$47,641
														Subtotal = $476,413

Issue Date FY: 2021 ( Subtotal = $476,413 )
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	2	4/29/2021	NON-COMPETING CONTINUATION	$47,641
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	2	4/26/2021	NON-COMPETING CONTINUATION	$428,772
														Subtotal = $476,413

Issue Date FY: 2020 ( Subtotal = $498,854 )
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	1	1/29/2020	NEW	$498,854
														Subtotal = $498,854

Grand Total All Awards = $2,404,506

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Temporal Processing by Growth Factors in Memory Formation

Award Number: R01MH120300

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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